EP0012201B2

EP0012201B2 - Coupling of aryl and heteroaryl monochlorides

Info

Publication number: EP0012201B2
Application number: EP79104204A
Authority: EP
Inventors: Ismael Colon; Louis Michael Maresca; George Thomas Kwiatkowski
Original assignee: BP Corp North America Inc
Current assignee: BP Corp North America Inc
Priority date: 1978-10-30
Filing date: 1979-10-29
Publication date: 1992-07-22
Anticipated expiration: 1999-10-29
Also published as: DE2967514D1; EP0012201B1; US4263466A; EP0012201A2; EP0131936A1; CA1127621A; EP0012201A3; EP0131936B1

Description

This invention pertains to a method of coupling aryl and heteroaryl mono chlorides and more particularly to the use of a catalyst mixture of an anhydrous nickel compound and a ligand in the presence of a reducing metal in a dipolar aprotic solvent.
Reactions which form carbon-carbon bonds are few although they are extremely useful in organic synthesis. In the formation of these bonds involving aryl groups, coupling is usually accomplished through the use of a metal. The use of copper in the Ullman reaction is described in Chem. Rev. 38,139 (1946); 64, 613 (1964). The use of nickel complexes was described by M. F. Semmelhack, et al in J. Am. Chem. Soc., 93, 5908 (1971). The use of palladium complexes was described by F. R. S. Clark, et al, J. Chem. Soc. Perkin I, 121 (1975). The latter reactions with nickel or palladium complexes have the advantage of proceeding at moderate temperatures but are disadvantageous in that aryl chlorides were either completely unreactive or gave very poor yields.
In Tetrahedron Letters No. 47, pages 4089 to 4092 (1977) the homo coupling of aryl and alkenyl halides is described. Actually, the examples deal only with the homo coupling of bromides and nothing is said about the possibility for coupling corresponding chlorides.
In J. Am. Chem. Soc. 1971, pages 5908 to 5910 it is described that only bromo or iodo compounds give satisfying yields when coupled in the presence of O-valent nickel compounds. By this reference, a prejudice was created to use chloro compounds in case O-valent nickel is used as catalyst in corresponding reactions. It was therefore unobvious that by carrying out corresponding coupling reactions in the presence of catalytically active compositions prepared in situ, a new process is provided which yields the final products in very high yields, sometimes in quantitative yields. These yields are higher than those described in the above mentioned publications.
The process of the present invention for coupling aryl and heteroaryl mono halides having 4 to 30 carbons by which said mono halides are contacted in an aprotic solvent, with a catalytically active composition which is prepared from an anhydrous nickel compound and at least one ligand selected from a triaryl phoisphine having 6 to 14 carbons in each aryl moiety and an aromatic bidentate compound containing at least one ring nitrogen atom and 5 to 30 carbon atoms and mixtures thereof and a reducing metal selected from zinc, magnesium and manganese, at a temperature of 0 to 250°C, optionally in the presence of at least 0.1 moles per gram atom of nickel of an inorganic salt as a promotor, the catalytically active composition being formed in situ, the ratio of gram atoms of nickel to moles of aryl or heteroaryl mono halide being in the range of 0.0001 to 0.5, the amount of ligand being 0.1 to 100 moles per gram atom of nickel and the amount of reducing metal being at least 1 gram atom per mole of reacted aryl or heteroaryl mono halide, is characterized in that aryl and heteroaryl mono chlorides are used as starting halides.
The coupled products of this invention can be used as heat transfer media, liquid crystal intermediates, fluorescent brighteners, or polymer additives.
The coupling reaction most preferably takes place at temperatures form 40 to 80°C. Pressure is not critical and so superatmospheric or subatmospheric pressures can be used as well as atmospheric pressure. Reaction is carried out in an inert atmosphere.
Reaction time is not critical since quantitative yields are often obtained in less than 2 hours. When inorganic salt promotors are used, reaction times of only a few minutes are required to achieve high yields of coupled aryl compounds. These are no maximum times since the reaction is essentially irreversible.
Preferred promotors include alkali, alkaline earth, zinc, magnesium, manganese and aluminium halides, sulfates or phosphates or mixtures thereof. Iodides are particularly preferred. The amount of promotor, when used, can range from 0.1 to 1000 moles per gram atom of nickel with 1 to 100 moles of promotor being preferred.
Suitable nickel compounds are those reducible by organometallic and metal reducing agents. These compounds include nickel halides, that is, the chlorides, bromides and iodides, nickel sulfates, nickel phosphates, nickel carbonates, nickel salts of organic acids having 1 to 18 carbons, such as, nickel formate, nickel acetate, and nickel organic complexes such as nickel acetylacetone, dichloro-bis(triphenylphosphine) nickel (II); and nickel (O) compounds such as bis(1,5-cyclooctadiene) nickel and tetrakis(triphenylphosphine) nickel. The anion of the nickel compounds is unimportant and serves merely to provide nickel ion to the catalyst mixture, but it must not interfere with the reaction of the nickel compound with the ligand. The preferred anions are the halides, especially nickel chloride.
Suitable triaryl phosphines include triphenylphosphine, triphenylphosphines containing alkyl oralkoxy substituents having up to 8 carbon atoms, and unsubstituted or alkyl- and alkoxy-substituted trinaphthylphos- phines. Suitable bidentate compounds include 2,2'-bipyridyl, 1,10-phenanthroline, 1,8-naphthyridine or 2-methylaminopyridine. Also a mixture of triphenylphosphine and 2,2'-bipyridine may be used.
Preferred aprotic solvents include dipolar solvents, such as dimethylacetamide, dimethylformamide, dimethylsulfoxide or sulfolane. If desired these aprotic solvents can be mixed with lower polarity inert solvents, such as saturated aliphatic hydrocarbons, including pentanes, hexanes ordodecanes; aromatic hydrocarbons, such as, benzene, toluene, xylenes; and saturated aliphatic and cycloaliphatic ethers, such as, diethyl ether, diglyme or tetrahydrofuran.
It is preferred that all solvents used in the practice of this invention be anhydrous.
Although magnesium and manganese metals can be used, zinc metal is the preferred metal in the process for coupling aryl mono chlorides. It is also preferred that the metal be in finely divided form with an average size of 0.833 mm or finer when measures on the U.S. sieve scale (mesh size 20 or less).
Preparation of the catalyst composition is carried out conveniently by mixing the aforementioned nickel compound, ligand(s), promotor, magnesium and/or manganese metals in the aprotic solvent under an inert atmosphere and heating from 25 to 60.C.
While not wishing to be bound by any scientific theory or explanation of the mechanism of the coupling reaction of this invention, it is believed that the combination of nickel compound, ligand and reducing metal provides nickel in a zero valent state, a form which in an anhydrous aprotic medium enables the coupling of aryl mono chlorides to take place in excellent yields.
The nickel (O) ligand complex believed to be the active catalyst can be formed in situ in the presence of an aryl chloride, or the catalyst can be performed in situ prior to the addition of the aryl chloride. A method for the determination of zero valent nickel is described by C. A. Tolman, J. Am. Chem. Soc. 92, 2956 (1970). The preferred ratio of gram atoms of nickel to moles of aryl chloride is 0.001 to 0.1. The preferred ratio of ligand to nickel is 1 to 30 moles per gram atom of nickel.
The preferred aryl mono chlorides used in this invention have the formula (I):
wherein R is independently selected from a monovalent inert radical such as alkyl, aryl, F, unsubstituted or substituted amino, -CN, -CHO, -Oaryl, -Oalkyl, -OCOaryl, -OCOalkyl, -COOalkyl, -COOaryl,
―SO₂―aryl or―SO₂―alkyl, ―SO₃―alkyl and ―SO₃aryl wherein the aryl contains 4 to 30 carbon atoms, the alkyl contains 1 to 8 carbon atoms and a is an integer having values of 0 to 4, with the proviso that no more than one R is in a position ortho to the CI-Linked ring carbon atom. By inert radicals is meant radicals which do not interfere with the coupling reaction.
Another preferred mono chloride compound is a heteroaryl mono chloride wherein one or more of the carbon atoms of the benzene ring in formula (I) is replaced by a hetero atom such as N or P. Preferred aryl mono- chlorides are 2-chloropyridine and compounds of formula (I) in which R=CH₃COO- or CH:r- and a is 1.
The invention is further described in the examples which follow. All parts and percentages are by weight unless otherwise specified.

Example 1

In a 50 ml flask were placed 0.13 g of anhydrous nickel chloride, 2.0 g triphenylphosphine, and 2.0 g of zinc dust, which had been treated by washing with warm acetic acid then ether and dried on a vacuum line. The flask was sealed with a serum cap and purged with nitrogen for 30 minutes. Ten mls of dry DMAC (dimethylacetamide) was added and the flask was placed in an oil bath at 80°C. The solution was stirred by a magnetic bar and once the red-brown nickel (0) complex had formed, 2 ml of dry chlorobenzene were added. After 90 minutes the chlorobenzene had been converted quantitatively to biphenyl as determined by gas chromatography using toluene as an internal standard.

Examples 2-8

The following experiments were carried out according to Example 1, but 0.01 moles of the various promotor salts listed in Table 1 were also included.
Compared to Example 1 it is seen in Example 2-8 that addition of the promotor salts reduces the reaction time by as much as a factor of 20 while maintaining essentially quantitative yields.

Examples 9-10

The following examples were carried out in accordance with Example 1 except that zinc was replaced by the metal listed in Table 2.

Examples 11-17

The following examples were carried out in accordance with Example 1 except that the substituted chlorobenzenes listed in Tabvle 3 were used in place of chlorobenzene. Any additives not found in Example 1 are also included in table 3.
It should be noted that in Examples 11-13 multiple products were obtained. These are listed in Table 4.

Examples 18-21

The following experiments were performed in accordance with Example 1 except that nickel chloride was replaced by the nickel salts listed in Table 5 and 0.01 moles of Nal were included.

Example 22

Example 1 was repeated with the exception that the triphenylphosphine was replaced by an equivalent amount of tris(p-methoxyphenyl) phosphine. A 89% yield of biphenyl was obtained in 2 hours.

Examples 23-27

The following examples illustrate the use of an aromatic bidentate nitrogen compound in the coupling reaction.

Example 23

0.13 g NiCl₂, 2.0 g zinc, 2.0 g triphenylphosphine, 1.0 g sodium iodide, and 0.2 g 2,2'-bipyridine were added to in a 50 ml flask. The flask was evacuated and filled with nitrogen and then 10 ml of dry DMAC and 2 ml p-chloroanisole were added. The reaction mixture was then stirred and reacted at 80°C. After 75 min. the reaction was over as determined by disappearance of p-chloroanisole, and a 80% yield of 4,4'-dimethoxybiphenyl was obtained. In contrast to example number 13, a higher yield of coupled product was obtained and there were no other biphenyls produced. The addition of bipyridine appears to suppress the side reaction leading to these other poroducts. The only other significant product produced was anisole.

Example 24

0.13 g NiCl₂, 2.0 g Zn, 1.0 g triphenylphosphine, and 0.16 g 2,2'-bipyridine were placed in a 50 ml flask. The flask was evacuated and filled with nitrogen and then 15 ml of dry DMAC and 2 ml of p-chloroanisole were added. The mixture was stirred and reacted at 70°C for 45 minutes. Gas chromatographic analysis of the mixture revealed 3.4% anisole, 96.4% dimethoxybiphenyl, and a trace (0.2%) of p-chloroanisole. In contrast to Example 13, a higher yield of coupled product was obtained and there were no other biphenyls produced. The reaction was also faster (45 vs. 90 minutes).

Example 25

This example illustrates the use of 2-methylaminopyridine to suppress formation of the monosubstituted product. To a mixture of 0.13 g nickel chloride, 0.8 g triphenylphosphine, 2.0 g zinc dust, and 1.0 g sodium bromide in a 50 ml flask, 10 ml DMF (dimethylformamide) and 0.2 ml 2-methylaminopyridine were added under a nitrogen atmosphere. This mixture was reacted for several minutes at 70°C and then 2 ml p-chloroanisole were added. After 5 hours at 70°C gas chromatographic analysis of the reaction mixture revealed: anisole (34.5%), p-chloroanisole (1.4%) and 4,4'-di-methoxybiphenyl (62.9%). There was also a trace of other biphenyls.

Example 26

This Example illustrates that bipyridine can be generated in situ and is as effective at suppressing the mono-substituted product as adding bipyridine to the initial catalyst mixture. To a 50 ml flask were added 0.13 g nickel chloride, 1.0 g triphenylphosphine, 1.0 g sodium bromide and 2.5 g zinc dust. The flask was sealed, evacuated, and then filled with nitrogen. Fifteen ml of dry DMAC were added through a serum cap and the solution was stirred at 70°C for several minutes. Two-tenths ml of 2-chloropyridine was added (through the serum cap) and reacted for 45 mins. Two mls of p-chloroanisole were then added and reacted for 2 hours. Gas chromatographic analysis after this period revealed: anisole (7.4%), 4-methoxybiphenyl (0.3%) and 4,4'-dimethoxybiphenyl (92.3%).

Example 27

This Example illustrates that a triaryl phosphine need not be present for the coupling reaction to occur, and that bipyridine can be used in its place.
In a 50 ml flask were placed 0.13 g NiCl₂. 2.0 Zn, 1.0 g Nal, and 0.62 g bipyridine. After evacuation and filling with nitrogen, 10 ml dry DMAC were added along with 2 ml chlorobenzene. The mixture was stirred and reacted at 80°C. After 48 hours there was 78 percent conversion of chlorobenzene to biphenyl.
Although the invention has been described in its preferred form with a certain degree of particularity, it is understood that the present disclosure has been made only by way of example.

Claims

1. A method for coupling aryl and heteroaryl mono halides having 4 to 30 carbons by which said mono halides are contacted in an aprotic solvent, with a catalytically active composition which is prepared from an anhydrous nickel compound and at least one ligand selected from a triaryl phosphine having 6 to 14 carbons in each aryl moiety and an aromatic bidentate compound containing at least one ring nitrogen atom and 5 to 30 carbon atoms and mixtures thereof and a reducing metal selected from zinc, magnesium and manganese, at a temperature of 0 to 250°C, preferably 25 to 125°C, optionally in the presence of at least 0.1 moles per gram atom of nickel of an inorganic salt as a promotor, the catalytically active composition being formed in situ, the ratio of gram atoms of nickel to moles of aryl or heteroaryl mono halide being in the range of 0.00001 to 0.5, the amount of ligand being 0.1 to 100 moles per gram atom of nickel and the amount of reducing metal being at least 1 gram atom per mole of reacted aryl or heteroaryl mono halide, characterized in that aryl and heteroaryl mono chlorides are used as starting halides.

2. A method as claimed in claim 1 wherein the reducing metal is a finely divided powder having a particle size of 0.833 mm or finer.

3. A method as claimed in claim 1 or 2 wherein the nickel compound is nickel chloride.

4. A method as claimed in any of claims 1 to 3 wherein the ligand is triphenylphosphine, 2,2'-bipyridine or a mixture of both.

5. A method as claimed in any one of claims 1 to 4 wherein the promotor is an alkali metal iodide, bromide or chloride.

6. A method as claimed in any one of claims 1 to 5 wherein the aprotic solvent is dimethylacetamide or dimethylformamide.

7. A method as claimed in any one of claims 1 to 6 wherein the aryl mono chloride has the formula (I):

wherein R is a monovalent inert radical selected from alkyl, aryl, F, unsubstituted or substituted amino, -CN, -CHO, -Oaryl, -Oalkyl, -OCO-alkyl, -OCOaryl, -COOalkyl, -COOaryl,

―SO₂―alkyl, -S0₂aryl, -S0₃alkyl and -S0₃aryl wherein the aryl contains 4 to 30 carbons, the alkyl contains 1 to 8 carbons and a is an integer having values of 0 to 4 with the proviso that no more than one R is in a position ortho to the Cl linked ring carbon atom.

8. A method as defined in claim 7 wherein one or more of the carbon atoms of the benzene ring in formula (I) is replaced by N or P.

9. A method as claimed in claim 8 wherein the aryl chloride is 2-chloropyridine.

10. A method as claimed in claims 7 or 8 wherein R is methyl or CH₃CO₂― and a is 1.